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Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP
The transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positive...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231326/ https://www.ncbi.nlm.nih.gov/pubmed/30404014 http://dx.doi.org/10.1016/j.celrep.2018.10.024 |
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author | Moreno-Vicente, Roberto Pavón, Dácil María Martín-Padura, Inés Català-Montoro, Mauro Díez-Sánchez, Alberto Quílez-Álvarez, Antonio López, Juan Antonio Sánchez-Álvarez, Miguel Vázquez, Jesús Strippoli, Raffaele del Pozo, Miguel A. |
author_facet | Moreno-Vicente, Roberto Pavón, Dácil María Martín-Padura, Inés Català-Montoro, Mauro Díez-Sánchez, Alberto Quílez-Álvarez, Antonio López, Juan Antonio Sánchez-Álvarez, Miguel Vázquez, Jesús Strippoli, Raffaele del Pozo, Miguel A. |
author_sort | Moreno-Vicente, Roberto |
collection | PubMed |
description | The transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin-cytoskeleton-dependent and Hippo-kinase-independent mechanisms. RHO activity is necessary, but not sufficient, for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based small interfering RNA (siRNA) screens provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective extracellular matrix (ECM) remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications. |
format | Online Article Text |
id | pubmed-6231326 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-62313262018-11-19 Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP Moreno-Vicente, Roberto Pavón, Dácil María Martín-Padura, Inés Català-Montoro, Mauro Díez-Sánchez, Alberto Quílez-Álvarez, Antonio López, Juan Antonio Sánchez-Álvarez, Miguel Vázquez, Jesús Strippoli, Raffaele del Pozo, Miguel A. Cell Rep Article The transcriptional regulator YAP orchestrates many cellular functions, including tissue homeostasis, organ growth control, and tumorigenesis. Mechanical stimuli are a key input to YAP activity, but the mechanisms controlling this regulation remain largely uncharacterized. We show that CAV1 positively modulates the YAP mechanoresponse to substrate stiffness through actin-cytoskeleton-dependent and Hippo-kinase-independent mechanisms. RHO activity is necessary, but not sufficient, for CAV1-dependent mechanoregulation of YAP activity. Systematic quantitative interactomic studies and image-based small interfering RNA (siRNA) screens provide evidence that this actin-dependent regulation is determined by YAP interaction with the 14-3-3 protein YWHAH. Constitutive YAP activation rescued phenotypes associated with CAV1 loss, including defective extracellular matrix (ECM) remodeling. CAV1-mediated control of YAP activity was validated in vivo in a model of pancreatitis-driven acinar-to-ductal metaplasia. We propose that this CAV1-YAP mechanotransduction system controls a significant share of cell programs linked to these two pivotal regulators, with potentially broad physiological and pathological implications. Cell Press 2018-11-06 /pmc/articles/PMC6231326/ /pubmed/30404014 http://dx.doi.org/10.1016/j.celrep.2018.10.024 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Moreno-Vicente, Roberto Pavón, Dácil María Martín-Padura, Inés Català-Montoro, Mauro Díez-Sánchez, Alberto Quílez-Álvarez, Antonio López, Juan Antonio Sánchez-Álvarez, Miguel Vázquez, Jesús Strippoli, Raffaele del Pozo, Miguel A. Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP |
title | Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP |
title_full | Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP |
title_fullStr | Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP |
title_full_unstemmed | Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP |
title_short | Caveolin-1 Modulates Mechanotransduction Responses to Substrate Stiffness through Actin-Dependent Control of YAP |
title_sort | caveolin-1 modulates mechanotransduction responses to substrate stiffness through actin-dependent control of yap |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6231326/ https://www.ncbi.nlm.nih.gov/pubmed/30404014 http://dx.doi.org/10.1016/j.celrep.2018.10.024 |
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